Convenient synthesis of 3,5-disubstituted isoxazoles

Article abstract of DOI:10.1080/00397910601055107

α,β-Unsaturated oximes obtained from the corresponding α,β-unsaturated ketones on treatment with 2 equivalents of manganese dioxide in refluxing chloroform gives 3,5-disubstituted isoxazoles in good yields. Copyright Taylor & Francis Group, LLC.

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Convenient Synthesis of 3,5‐Disubstituted
Isoxazoles
Reshma F. Kurangi a , Rima Kawthankar b , Sulfala Sawal b , Vidya G. Desai b
& Santosh G. Tilve a
a Department of Chemistry, Goa University, Goa, India
b Department of Chemistry, Dnyanprassarak Mandal's College of Arts,
Science, and Commerce, Assagao, Mapusa, Bardez, Goa, India
Version of record first published: 06 Mar 2007.
To cite this article: Reshma F. Kurangi , Rima Kawthankar , Sulfala Sawal , Vidya G. Desai & Santosh G. Tilve
(2007): Convenient Synthesis of 3,5‐Disubstituted Isoxazoles, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 37:4, 585-587
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Synthetic Communicationsw, 37: 585–587, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910601055107
Convenient Synthesis
of 3,5-Disubstituted Isoxazoles
Reshma F. Kurangi
Department of Chemistry, Goa University, Goa, India
Rima Kawthankar, Sulfala Sawal, and Vidya G. Desai
Department of Chemistry, Dnyanprassarak Mandal’s College of Arts,
Science, and Commerce, Assagao, Mapusa, Bardez, Goa, India
Santosh G. Tilve
Department of Chemistry, Goa University, Goa, India
Abstract: a,b-Unsaturated oximes obtained from the corresponding a,b-unsaturated
ketones on treatment with 2 equivalents of manganese dioxide in refluxing chloroform
gives 3,5-disubstituted isoxazoles in good yields.
Keywords: heterocycle, isoxazole, MnO2, oxidative cyclisation
Isoxazoles[1] form an important class of aromatic heterocycles and have
diverse applications. Their range of uses includes medicinal, herbicidal, fun-
gicidal, pesticidal applications; dyes; insulating oils and lubricants. Isoxazoles
contain a weak nitrogen–oxygen bond, which has been exploited to provide
difunctionalized compounds such as 1,3-dicarbonyl, enaminoketone, g-ami-
noalcohols, and b-hydroxy ketone. Thus, isoxazoles serve as building
blocks in organic synthesis.
Earlier, we had reported dichloro dicyano benzoquinone (DDQ) as an
oxidative cyclizing agent for the synthesis of 3,5-diaryl isoxazoles from the
oximes of corresponding ketones.[2] Recently, MnO2 has been used as a
Received July 12, 2006
Address correspondence to Vidya G. Desai, Department of Chemistry, Dnyanpras-
sarak Mandal’s College of Arts, Science, and Commerce, Assagao, Mapusa, Bardez,
Goa 403 507, India. E-mail: vidchem@gmx.net
585

586
R. F. Kurangi et al.
Scheme 1.
tandem oxidation process (TOP) agent[3] in a variety of synthetic manipula-
tions including synthesis of heterocycles. Because MnO2 is a mild,
nontoxic, and cheaply available reagent, we thought of using this for the
synthesis of isoxazoles (Scheme 1). Our initial attempt at oxidative cyclisation
of the chalcone oxime 1a in CH2Cl2 failed. When refluxing chloroform was
used, we could get the corresponding 3,5-diphenyl isoxazole (2a) in 60%
yield after 2 h. Similarly the other unsaturated oximes (Table 1, entries
2a–j) yielded the corresponding isoxazoles. To check the feasibility of the
TOP sequence,[3] a mixture of chalcone 1a, MnO2, NH2OH HCl, and tri-
.
ethylamine (TEA) in refluxing CHCl3 was attempted, but without success.
When tetrahydrofuran (THF) was used as a solvent, some amount of direct
formation of product was observed, but under the varying conditions tried,
complete conversion could not be obtained. However, it was possible to
obtain the isoxazole in a one-pot experiment wherein initially chalcone 1a,
.
3 equivalents of NH2OH HCl, and 3 equivalents of TEA were stirred for
30 min, followed by the addition of MnO2 (5 equivalents) and refluxing for 2 h.
In conclusion, we have developed a convenient method for the synthesis of
3,5-disubstituted isoxazoles from a,b-unsaturated ketones. The procedure works
well for differently substituted 3,5-diaryl isoxazoles (Table 1, entries 2a–h). It
also works well when one of the group is alkyl (entries 2i–j). It fails to work
when both the groups are alkyl and also with a,b-unsaturated aldehydes or
Table 1. Preparation of 3,5-disubstituted isoxazoles 3a-j
Compound
1–3
Yield of
3 (%)
Mp (8C)
(lit.mp)
R1
R2
a
b
c
d
e
f
Ph
Ph
Ph
Ph
Ph
Ph
67
62
69
75
65
79
65
60
70
75
141 (140–141[4]
)
4-MeOC6H4
4-ClC6H4
4-BrC6H4
4-NO2C6H4
4-ClC6H4
4-BrC6H4
4-NO2C6H4
CH3
122 (122[5]
)
175 (172–178[6]
178 (178–180[6]
228 (226–228[7]
)
)
)
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
Ph
209 (210[7]
)
g
h
i
130 (130–132[6]
175 (172–175[6]
)
)
67 (67[8]
)
j
4-MeOC6H4
CH3
113 (111–112[9]
)

3,5-Disubstituted Isoxazoles
587
their oximes. Also, extending the method for the one-pot synthesis of corre-
sponding pyrazoles using hydrazine did not work well in our hands.
EXPERIMENTAL
All melting points are uncorrected and were measured by the normal Thiels
tube (paraffin) method. Column chromatography was performed on silica
gel G (13% CaSO4 as binder). IR spectra were recorded on a Shimadzu
FT-IR spectrophotometer (KBr pellets). 1H NMR and 13CMR were
recorded on a Brucker 300-MHz instrument. The multiplicities of carbon
signals were obtained from distortionless enhancement by polarization
transfer (DEPT) experiments.
General Procedure
A mixture of a,b-unsaturated oxime 2 (1 mmol), MnO2 (2 mmol), and chloro-
form (15 mL) was refluxed for 2 h (or until the reaction was completed). After
cooling, it was filtered and the black residue was washed with chloroform
(5 Â 5 mL). The combined filtrate after concentration was further purified
by passing through a small column of silica gel using ethyl acetate–hexane
(5:95) as an eluent.
ACKNOWLEDGMENT
We thank the University Grants Commission for financial assistance and the
National Institute of Oceanography, Goa, for spectral analysis.
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